Adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, and preterm birth, continue to be significant sources of perinatal morbidity and mortality, as well as adult diseases with fetal origin. Currently, there is an urgent need to develop a clinically useful and accurate early predictor of these adverse outcomes so that clinical care can be optimized. Furthermore, the success of future investigative efforts exploring therapies aimed at preventing these adverse outcomes is largely dependent on the early identification of those pregnancies at greatest risk. Abnormalities in trophoblastic invasion and early placental development have been implicated in the pathogenesis of preeclampsia, fetal growth restriction, spontaneous preterm birth and stillbirth. Moreover, as trophoblastic invasion is largely completed by the end of the first trimester, ultrasound-based biomarkers of early placental development are appealing candidates for predictors of adverse outcomes. Until recently, research in this area has been relegated to indirect measures of early placental development, such as uterine artery Doppler. However, recent advances in 3-dimensional sonography have allowed investigators to assess early gross placental development in a more direct manner. We have recently proposed a placental morphology index (PMI) which considers fetal size, placental volume and mean placental diameter as a means of discriminating between various components of gross placental morphology. In fact, our pilot data support PMI measured at 11-14 weeks as a significant predictor of adverse pregnancy outcomes. In this research proposal, we aim to examine the utility of our novel sonographic placental measures in the prediction of adverse pregnancy outcomes. Furthermore, to supplement our 3- dimensional sonographic measures while remaining consistent with our placenta-specific approach, we will examine the utility of combining our gross placental measures with promising serum biomarkers of placental development. Two such promising analytes, placental growth factor and placenta protein 13, are specifically expressed by the placenta and play critical roles in early placental development. Moreover, they have shown significant predictive value for the occurrence of adverse pregnancy outcomes, even as early as the first trimester. Thus, it is our hypothesis that the combination of our 3-dimensional measures of gross placental development with placental analytes known to be indicators of trophoblastic invasion can yield an early 'placental profile' that can identify pregnancies at greatest risk for adverse pregnancy outcomes long before the clinical manifestations arise. In this research endeavor, we will obtain 3-dimensional ultrasound volume sets of the placenta at 11-14 weeks, as well as a maternal serum sample, as part of a prospective cohort study aimed at developing an early screening test for the prediction of adverse pregnancy outcomes. PUBLIC HEALTH RELEVANCE: The placental plays a central role in many adverse pregnancy outcomes, such as preeclampsia, fetal growth restriction, and perinatal death. This study will explore the ability of 3-dimensional ultrasound measures of early placental development to predict these adverse outcomes in combination with maternal blood levels of two placental proteins, placental growth factor and placental protein 13, which have been associated with both placental development and adverse pregnancy outcomes. Our goal is to develop a screening test that can identify high risk pregnancies early in gestation so that their pregnancy management can be optimized.